HLA-A*32:01 Linked to Lamotrigine-Induced DRESS

HLA-A*32:01 was strongly associated with lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in a multicenter US matched case-control study published in JAMA Network Open. The authors said adding the allele to commercial pharmacogenomic panels could improve preprescription risk identification.

Investigators enrolled 29 patients with RegiSCAR-confirmed lamotrigine-induced DRESS at 2 US academic centers from April 2016 through June 2025. They selected 290 lamotrigine-tolerant controls from the BioVU biobank and matched them 10:1 to cases by age, sex, and self-reported race. Cases underwent high-resolution HLA typing, whereas control alleles were imputed from genotyping-array data; associations were assessed by logistic regression with Bonferroni correction.

HLA-A32:01 was present in 12 of 29 cases (41.4%) and 12 of 290 controls (4.1%) (odds ratio [OR], 16.4; Bonferroni-corrected P<.001). No other class I alleles or class II loci remained significantly associated after correction for multiple testing. The A32:01~B*44:02 haplotype was also enriched among cases (OR, 18.4; Bonferroni-corrected P=.001).

Acute liver injury occurred in 20 cases (69.0%) and did not differ significantly between allele carriers and noncarriers (75.0% vs 64.7%; P=.69). HLA-A31:01 was not enriched among cases, and HLA-B15:02 was found in neither group.

Limitations included the small case cohort, its predominantly US White composition, and use of imputed HLA data for controls versus high-resolution typing for cases. The study was underpowered for moderate associations or lower-frequency alleles. Because HLA-A*32:01 occurred in fewer than half of cases, it was neither necessary nor sufficient for DRESS. Investigators called for validation in more diverse cohorts and said its relevance to Stevens-Johnson syndrome/toxic epidermal necrolysis remains unknown.

Source: Krantz MS, Zhou L, Wang L, et al. HLA-A*32:01 and lamotrigine-induced drug reaction with eosinophilia and systemic symptoms. JAMA Netw Open. 2026;9(9):e2631291. doi:10.1001/jamanetworkopen.2026.31291